Preparation of highly stable concentrated dispersions of silver nanoparticles using synergistic dispersing agents

ABSTRACT

Methods for preparing highly stable concentrated dispersions of silver nanoparticles and described herein. Contemplated methods comprise combining a selected polysaccharidic dispersant with a selected non-reacting dispersant to yield concentrated silver dispersions with enhanced stability and lowered undesirable residual organics. Contemplated methods further comprise selecting an appropriate source of silver ions to reduce the ionic strength of the reaction medium and final silver dispersions.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. patent applicationwith Ser. No. 16/879,697, which was filed May 20, 2020, which claimspriority to U.S. provisional patent application with Ser. No.63/001,127, which was filed Mar. 27, 2020. This and all other extrinsicmaterials discussed herein are incorporated by reference in theirentirety. Where a definition or use of a term in an incorporatedreference is inconsistent or contrary to the definition of that termprovided herein, the definition of that term provided herein applies andthe definition of the term in the reference does not apply.

FIELD OF THE INVENTION

The field of the invention is silver nanoparticle dispersions andmethods of preparing silver nanoparticle dispersions.

BACKGROUND

Silver nanoparticles have unique properties that make them suitable forincorporation into a growing number of products ranging from biologicaland chemical sensors, conductive inks, pastes and filler. Silvernanoparticles are also used in antimicrobial coatings, biomedicaldevices, photonic devices and molecular diagnostics.

In the preparation of silver nanoparticles, polymeric dispersants areeffective additives for preventing particles aggregation in liquidmedia. While very dilute silver sols (<0.01 mol/L Ag) can be prepared inabsence of dispersants, in concentrated systems they are necessary toprevent the particles aggregation due to the high ionic strength.

The outstanding effectiveness of polymeric extracts obtained from plants(‘gums’) and animals (gelatin) for certain uses has been widelyexploited since antiquity and validated by many recent systematicscientific studies. Having a high solubility in water, polymericextracts obtained from plants and animals are excellent choices forpreparing a wide variety of aqueous colloidal systems including silversols. Their outstanding ‘colloid protective’ capacity is primarily dueto their large molecules, which are more effective in screening theinterparticles attractive forces (primarily Van der Waals).

In general, dispersing agents are used strictly as ‘protective colloids’in combination with dedicated reducing agents capable of reducing silverions/salts (glucose, hydrazine, ascorbic acid, hydroxylamine, etc.). Aspolymeric polysaccharides incorporate sugar moieties in their molecule,they have reducing properties as well. Indeed, in selected reactionconditions it was shown that polymeric polysaccharides can yield certainstable dispersions of silver nanoparticles in absence of a dedicatedreductant. See Goia et al., U.S. Pat. No. 7,842,274; Goia D. V.,Balantrapu, K., Journal of Materials Research 24, 9 (2009) 2828-2836.

U.S. Pat. No. 7,842,274 teaches preparation of silver-based particlesand electrical contact materials. The silver nanoparticles were preparedby adding an AgNO₃ solution and a NaOH solution under strong agitationin a reaction vessel containing an aqueous solution of a polysaccharide.An Ag(+1)-oxide species was generated, and the temperature was raisedand suspension stirred for 45 minutes. The resulting silvernanoparticles were separated from the mother liquor and washed with DIwater and ethanol. The particles were dried overnight and screenedthrough a mesh screen. Silver nanoparticles prepared using the methodsof the '274 patent were noted as having a medium silver particle size(TEM) of d50=20 nm, and a maximum particle size of d100=60 nm.

However, the inherent structural change in the polysaccharidemacromolecule following the loss of electrons tends to diminish theirdispersing efficiency. Consequently, a large excess of polysaccharidemust be added in the system to ensure the presence of sufficientunaltered polymer macromolecules capable of preventing particlesaggregation. The excess residual dispersant causes significant problemsduring the processing of silver nanoparticles and potential adverseeffects in many applications. Further, silver nanoparticles prepared inconnection with the '274 patent yield relatively large silvernanoparticles, which are undesirable from a toxicity perspective whenused in drug delivery.

The present disclosure is directed toward one or more improved featuresidentified below, and to methods and preparations that address theabove-mentioned problems.

SUMMARY OF THE INVENTION

The present invention is directed to a method of producing a highlystable, concentrated dispersion of silver nanoparticles. The methodcomprises dissolving a combination of a reducing dispersant and aco-dispersant in deionized water to form a first solution, and combiningthe first solution with at least one of a silver compound and a firstmixture prepared by adding a silver compound to deionized water. Themethod further comprises mixing the slurry with a basic solution to forman alkaline basic slurry, and heating the alkaline basic slurry to yieldhighly uniform silver nanoparticles. In some preferred aspects, thehighly uniform silver nanoparticles are all less than or equal to 25nanometers (nm) in size, or all less than or equal to 15 nm in size. Insome preferred aspects, the highly uniform silver nanoparticles are allbetween 5-25 nm in size, all between 5-15 nm in size, or all about 10nm. As used herein, the term “about” or “substantially” should beinterpreted broadly to mean within 10%.

The present invention is also directed to highly stable concentrateddispersions of silver nanoparticles. The highly stable concentrateddispersions can be prepared using a method as set forth herein. In somepreferred aspects, the silver nanoparticles of the highly stableconcentrated dispersion are all less than or equal to 25 nanometers (nm)in size, or all less than or equal to 15 nm in size. In some preferredaspects, the highly uniform silver nanoparticles are all between 5-25 nmin size, all between 5-15 nm in size, or all about 10 nm.

Contemplated uses for the silver nanoparticles and/or the highly stableconcentrated dispersions of silver nanoparticles include, among otherthings, use as antimicrobial, antiviral, anti-inflammatory, andanti-cancer agents, use as medical device coatings, optical sensors, andcosmetics.

Various objects, features, aspects and advantages of the presentinvention will become more apparent from the following detaileddescription of preferred embodiments of the invention.

BRIEF DESCRIPTION

The details of embodiments of the present disclosure can be gleaned inpart by study of the accompanying drawings, in which like referencenumerals refer to like parts, and in which:

FIG. 1 is a UV-Vis of a dilute aliquot obtained by diluting thedispersion of Example 1 100 times.

FIG. 2A shows a FESEM image of prepared Ag nanoparticles according toExample 1.

FIG. 2B shows a SEM with large particles obtained from a samplegenerated in the conditions in U.S. Pat. No. 7,842,274.

DETAILED DESCRIPTION

The inventor has discovered methods of producing a highly stable,concentrated dispersion of silver nanoparticles in which at least 80%,at least 85%, at least 90%, at least 95%, at least 99% or even 100% ofthe silver nanoparticles are under 100 nm, more preferably under 75 nm,more preferably under 50 nm, and even more preferably under 25 nm.Highly stable concentrated dispersions of silver nanoparticles, forexample, those prepared using the methods described herein, aredescribed.

The method comprises dissolving a combination of a reducing dispersantand a non-reactive co-dispersant in deionized water to form a firstsolution, and combining the first solution with at least one of a silvercompound and a first mixture prepared by adding a silver compound todeionized water. The method further comprises mixing the slurry with abasic solution to form an alkaline basic slurry, and heating thealkaline basic slurry to yield highly uniform silver nanoparticles.

The silver compound may comprise any suitable silver compounds useful toproduce silver nanoparticles. A preferred silver compound for themethods and dispersions described herein is silver oxide. An inventiveelement of the inventive subject matter is the reduction of the ionicstrength of the reaction medium and final silver dispersion by selectingan appropriate source of silver ions, for example, a silver oxide.

It should be appreciated that most precipitation processes start fromsilver nitrate as it is the most accessible, inexpensive, and convenientto work with. In the precipitation of concentrated silver sols, however,the nitrate ions inevitably generate a high ionic strength. As a result,a larger amount of dispersant is needed to prevent particle aggregation.To mitigate the negative effect of the ionic strength on colloidalstability, Applicant selected, as an example, purified silver oxide as astarting salt in the precipitation process. Since the nitrate ions arecompletely eliminated during the purification of the oxide, the system'sionic strength is drastically decreased and a smaller amount ofdispersant is required to provide colloid stability.

Another inventive element of the inventive subject matter is using areducing dispersant capable of effectively reducing silver ions with anon-reacting dispersant that is highly effective at very lowconcentrations. The approach advantageously yields concentrated silverdispersions with enhanced stability while significantly lowering theamount of undesirable residual organics by eliminating the need for alarge excess of reducing dispersant. Without wishing to be bound by anyparticular theory, it is believed that the use of a polysaccharidedispersant such as Arabic gum with a non-reacting dispersant such assodium alginate as described herein has a synergistic effect. Forexample, the combination may enhance the protective colloid ability ofthe non-reacting dispersant and/or reducing capabilities of reducingdispersant at lower amounts when compared to those components on theirown.

The criteria for selecting the reducing dispersant (e.g., a reducingpolysaccharide) may include the following. First, it should be capableof reducing completely the silver ions/salt for obvious practical andeconomic reasons. Secondly, the polysaccharide should reduce rapidly thesilver ions to ensure the fast nucleation needed to obtain small anduniform silver nanoparticles. Some selection criteria for reducingdispersants may be found in Goia, D. V., Journal of Materials Chemistry,14, (2004) 451-458.

Arabic gum was shown to be capable of reducing silver ions and rapidlyreducing silver ions to ensure the fast nucleation needed to obtainsmall and uniform silver nanoparticles, and is a suitable reducingdispersant. Other natural ‘gums’ (e.g., tragacanth) have similarstructural features and in suitable conditions are also effective andcontemplated herein, among other dispersants.

One criterion in selecting the second dispersant to be provided insmaller amounts may be its ability to provide, at lower concentrations,similar or better protective colloid efficiency than the reducingdispersant. In general, the stabilizing action improves with increasingdispersion viscosity. The salts of alginic acid belong to a class ofmacromolecular compounds known as viscosity builders. They create veryviscous aqueous solutions and can even form hydrogels in certainconditions. Due to its swelling properties, sodium alginate may be apreferred co-dispersant as it provides better colloid stabilizingefficiency at concentrations 10 to 15 times lower than Arabic gum. Othernon-reducing water soluble substances from this viscosity builderscategory, for example those that provide better colloid stabilizingefficiency at concentrations 5-20 or 10-15 times lower than thepolysaccharide dispersant, should be considered covered by the presentdisclosure, among other dispersants.

Another potential criterion in selecting the co-dispersant relates toits potential ability to alter the properties of the silver surface.Since the co-dispersant remains structurally unaffected during thereduction, it can be used to predictably modify the surface of thesilver through spontaneous physical or chemical attachment. Although thesuitability of the co-dispersant to provide the desired surfaceproperties (charge, functionality, etc.) for a specific applicationshould be evaluated separately, the concept embodied in this applicationremains the basis for such future discoveries.

In some contemplated aspects, the co-dispersant may be present at aconcentration of less than ⅛ a concentration of the reducing dispersant.Additionally or alternatively, the amount of the silver compound addedto the first solution (directly or with deionized water as a firstmixture) can be between 1.8-3 times an amount of the combination of thereducing dispersant and co-dispersant dissolved in water. Where a firstmixture of the silver compound is added to the first solution, thevolume of the first mixture can be between, for example, 1.5-2.5 thevolume of the first solution.

The basic solution added to form an alkaline basic slurry that is heatedto yield highly uniform silver nanoparticles can comprise, for example,sodium hydroxide (NaOH).

Below is an example of preparing highly stable concentrated dispersionsof silver nanoparticles in accordance with a method of the inventivesubject matter.

Example 1

24.6 g of freshly precipitated and thoroughly washed Ag₂O (equivalent of23.0 g Ag metal) are added to 200 mL deionized water in a 500 mL glassbeaker. Separately, 11.6 g Arabic gum (reducing dispersant) and 0.4 gsodium alginate (co-dispersant) are dissolved in 100 mL DI water for atleast one hour. The dispersant solution is added to the silver oxide andthe slurry is subjected for at least 20 more minutes to high shearmixing using a Dispermat-type device while ensuring the temperature doesnot exceed 50° C. Using 50 mL DI water, the content of the beaker istransferred quantitatively into a 2.0 L glass reactor provided with athree-blade propeller connected to a variable speed motor and heatingcapabilities. After adding 12.5 mL NaOH 10N and adjusting the volume ofthe slurry to 1.0 L with DI water, under vigorous mixing the temperatureof the dispersion is brought rapidly (over 20 minutes) to 65° C. whereis maintained for 30 minutes to convert the silver oxide to silvernanoparticles. The resulting silver dispersion contains 2.3% Ag. Forelectron microscopy analysis the Ag nanoparticles can be isolated byultracentrifugation. The UV-Vis analysis can be performed by dilutingthe final dispersion 100 times.

Product Data

FIG. 1 is a UV-Vis of a dilute aliquot obtained by diluting thedispersion of Example 1 100 times. The dark brown silver dispersioncontains highly dispersed silver nanoparticles as testified by theplasmon band recorded by the UV-Vis analysis. The narrow peak suggeststhe presence of highly uniform nanoparticles while the low backgroundabsorption (over 600 nm) indicates the absence of large silver entities.The stability of the dispersion was excellent as indicated by the lackof particles settling and changes in the UV-Vis spectrum after 360 days.

FIGS. 2A-2B show FESEM images of prepared Ag nanoparticles from presentdisclosure, Example 1 (FIG. 2A), and SEM with large particles obtainedfrom a sample generated in the conditions in U.S. Pat. No. 7,842,274(FIG. 2B).

The FESEM images (e.g., image shown in FIG. 2A) showed the presence ofuniform nanoparticles with an average size of ^(˜)10 nm and the absenceof larger particles or aggregates. As can be seen in comparing FIG. 2Ato FIG. 2B, there is a substantial improvement in particle uniformitythat was detected even though the specific consumption of reducingdispersant (g or Arabic gum per g silver) has been reduced by about 50%and replaced by a much smaller amount of the second, non-reactingdispersant.

Viewed from another perspective, even though a substantial amount ofArabic gum (e.g., 11.6 g instead of about 19-20 g) was replaced withonly 0.4 g of the co-dispersant alginate, a noticeable improvement isseen while reducing the overall amount of undesirable residual organicsat the same time. Viewed from yet another perspective, the use of twodispersants as described herein can result in a reduction in the totalamount of dispersant used (e.g., by between 25-60%, between 30-55%,between 35-45%) while showing greater or equal dispersion, stability,and/or uniformity.

The difference is particles uniformity is pronounced. The singledispersant procedure allow large particles (up to 40-50 nm or evenlarger) to form, as shown in FIG. 2B. In FIG. 2A, all of the silvernanoparticles are less than 25 nm in size (e.g., within 200% of 10 nm;about 10 nm).

Where the inventive subject matter is used in, for example,antimicrobial or antiviral applications, the two dispersants approachyielding highly uniform Ag particles around 10 nm (with no particleslarger than 15 nm) is advantageous since there is information in theliterature showing that, when used as a drug delivery vector, goldparticles/aggregates larger than 40 nm are accumulated in internalorgans and become toxic (in the case of silver the toxicity would likelymanifest as argyria). If this holds true, the silver colloidal of theinventive subject matter would be less prone to cause argyria. Further,there is information in the literature showing that only small particles(i.e., nonaggregated 33 nm or less) are cleared from the body. Althoughthe fate of colloidal gold particles was not evaluated in the currentstudies, several preclinical models suggest that the electrostaticallystabilized particles are taken up by hepatocytes (Hardonk et al. 1985;Renaud et al. 1989), not Kupffer cells, excreted into the bile andexpelled from the body in feces. Two key factors influence the clearanceof gold particles. First, smaller colloidal gold particles stabilizedwith either a protein or a polymer were preferentially taken up by thehepatocytes and ultimately excreted into the bile and eliminated in thefeces. See Id. Secondly, blocking Kupffer cell activity with gadoliniumchloride also increased the fraction of particles cleared by thehepatocytes. See Renaud et al. 1989. The size and RES-avoidingproperties of PT-cAu-TNF vector support similar mechanisms for clearanceof the particles.

Other Examples

It is contemplated that methods in accordance with the following may beused to prepare silver nanoparticle dispersions of the inventive subjectmatter. About 24.6 g of freshly precipitated and thoroughly washed Ag₂O(equivalent of about 23.0 g Ag metal) may be added to about 200 mLdeionized water in a 500 mL glass beaker. Separately, about 11.6 gArabic gum (reducing dispersant) and about 0.4 g sodium alginate(co-dispersant) may be dissolved in 100 mL DI water for any suitableamount of time, for example, at least one hour. The dispersant solutionmay be added to the silver oxide and the slurry may be subjected forabout 20-40 minutes (or longer) to high shear mixing using aDispermat-type device while ensuring the temperature does not exceedabout 50° C. Using about 50 mL DI water, the content of the beaker istransferred quantitatively into a 2.0 L glass reactor provided with athree-blade propeller connected to a variable speed motor and heatingcapabilities. After adding about 12.5 mL NaOH 10N and adjusting thevolume of the slurry to about 1.0 L with DI water, under vigorous mixingthe temperature of the dispersion is brought rapidly (over about 20-40minutes minutes) to about 65° C. where is maintained for about 30minutes to convert the silver oxide to silver nanoparticles. Theresulting silver dispersion may contain about 2.3% Ag. For electronmicroscopy analysis the Ag nanoparticles can be isolated byultracentrifugation. The UV-Vis analysis can be performed by dilutingthe final dispersion, for example, about 100 times.

It is also contemplated that methods in accordance with the followingmay be used to prepare silver nanoparticle dispersions of the inventivesubject matter. About 20-29.2 g of freshly precipitated and thoroughlywashed Ag₂O may be added to deionized water. Separately, about 8-15.2 gArabic gum (reducing dispersant) and about 0.1-1 g sodium alginate(co-dispersant) may be dissolved in DI water for any suitable amount oftime, for example, about an hour or at least one hour. The dispersantsolution may be added to the silver oxide and the slurry may besubjected for about 20-40 minutes (or any suitable amount of time) tohigh shear mixing using a Dispermat-type device while ensuring thetemperature does not exceed about 60° C., or more preferably about 50°C. Using DI water, the content of the beaker is transferred into a glassreactor provided with a three-blade propeller connected to a variablespeed motor and heating capabilities. After adding about 9-16 mL NaOHsolution and adjusting the volume of the slurry to about 0.5-1.5 L,about 1.0 L (or any other suitable volume) with DI water, under vigorousmixing the temperature of the dispersion is brought rapidly to about 65or between 55-75° C. where is maintained to convert the silver oxide tosilver nanoparticles. The resulting silver dispersion may contain about1.8-2.8% Ag.

Thus, specific embodiments and applications of methods of precipitatinghighly stable concentrated dispersions of silver nanoparticles have beendisclosed. It should be apparent, however, to those skilled in the artthat many more modifications besides those already described arepossible without departing from the inventive concepts herein. Theinventive subject matter, therefore, is not to be restricted except inthe spirit of the appended claims. Moreover, in interpreting both thespecification and the claims, all terms should be interpreted in thebroadest possible manner consistent with the context. In particular, theterms “comprises” and “comprising” should be interpreted as referring toelements, components, or steps in a non-exclusive manner, indicatingthat the referenced elements, components, or steps may be present, orutilized, or combined with other elements, components, or steps that arenot expressly referenced. Where the specification claims refers to atleast one of something selected from the group consisting of A, B, C . .. and N, the text should be interpreted as requiring only one elementfrom the group, not A plus N, or B plus N, etc.

Unless the context dictates the contrary, all ranges set forth hereinshould be interpreted as being inclusive of their endpoints andopen-ended ranges should be interpreted to include only commerciallypractical values. Similarly, all lists of values should be considered asinclusive of intermediate values unless the context indicates thecontrary. All methods described herein can be performed in any suitableorder unless otherwise indicated herein or otherwise clearlycontradicted by context. The use of any and all examples, or exemplarylanguage (e.g. “such as”) provided with respect to certain embodimentsherein is intended merely to better illuminate the invention and doesnot pose a limitation on the scope of the invention otherwise claimed.

As used in the description herein and throughout the claims that follow,the meaning of “a,” “an,” and “the” includes plural reference unless thecontext clearly dictates otherwise.

Groupings of alternative elements or embodiments of the inventiondisclosed herein are not to be construed as limitations. Each groupmember can be referred to and claimed individually or in any combinationwith other members of the group or other elements found herein. One ormore members of a group can be included in, or deleted from, a group forreasons of convenience and/or patentability. When any such inclusion ordeletion occurs, the specification is herein deemed to contain the groupas modified thus fulfilling the written description of all Markushgroups used in the appended claims.

What is claimed is:
 1. A highly stable concentrated dispersion of silvernanoparticles wherein no silver nanoparticle of the dispersion is largerthan 25 nm.
 2. A method of producing a highly stable concentrateddispersion of silver nanoparticles, comprising the steps of: dissolvinga combination of a reducing dispersant and co-dispersant in deionizedwater to form a first solution; adding silver oxide to the firstsolution to form a slurry; mixing the slurry with a basic solution; andheating the alkaline basic slurry to yield highly uniform silvernanoparticles wherein no silver nanoparticle is larger than 25 nm. 3.The method of claim 2, wherein the reducing dispersant comprises Arabicgum.
 4. The method of claim 2, wherein the co-dispersant is sodiumalginate.
 5. The method of claim 2, wherein no silver nanoparticle islarger than 15 nm.
 6. The method of claim 2, wherein the co-dispersantis present at a concentration of less than ⅛ a concentration of thereducing dispersant.
 7. The method of claim 2, wherein an amount of thesilver compound added to the deionized water to form the first mixtureis between 1.8-3 times an amount of the combination of the reducingdispersant and co-dispersant dissolved in water.
 8. The method of claim2, wherein the volume of the first mixture is between 1.5-2.5 the volumeof the first solution.
 9. The method of claim 2, wherein the basicsolution comprises NaOH.